The TRANSFORM-AF study has found that patients with atrial fibrillation (AF) and obesity who were treated with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) experienced a reduction in AF-related events—including hospitalisation, cardioversion and ablation for AF. This multicentre, pharmacoepidemiologic study was conducted across 170 Veterans Affairs hospitals in the USA and is among the first to evaluate the clinical effectiveness of GLP-1 RAs for secondary AF prevention in patients with both obesity and pre-existing AF.
Findings from the TRANSFORM-AF study were presented as a late-breaking clinical trial at the 2025 Heart Rhythm Society (HRS) annual meeting (24–27 April, San Diego, USA).
A HRS press release notes that, despite significant advancements in modern ablation techniques, the residual risk of AF recurrence remains at approximately 30% at one year and continues to rise cumulatively over time. This persistent risk is likely driven by inadequately managed cardiometabolic risk factors, with obesity being the most prevalent, the release adds, going on to state that—in the USA—more than 50% of patients undergoing AF ablation are classified as obese, underscoring the need for integrated strategies that target metabolic health alongside procedural interventions.
The TRANSFORM-AF study aimed to evaluate whether GLP-1 RAs, which are typically prescribed for diabetes, could reduce the burden of AF in patients with both AF and obesity.
This large, “robust” pharmacoepidemiologic study, involving 2,510 patients from Veterans Affairs medical centres across the USA, found that GLP-1 RA use was associated with a 13% reduction in major AF-related events, including hospitalisations for AF, cardioversions, and ablation procedures, during a median follow-up of three years.
Researchers also discovered that the benefits of the GLP-1 RAs were even greater for those with severe obesity (body mass index [BMI] >40)—and, “interestingly”, there was only an additional weight loss of 4% with diabetes management doses of GLP-1 RA, indicating a potential non-weight loss mediated effect of GLP-1 RA in AF.
“In patients with atrial fibrillation and obesity, the use of diabetic-dose GLP-1 receptor agonists was associated with improved AF-related outcomes, despite only a modest incremental weight loss,” said Varun Sundaram (Case Western Reserve University, Cleveland, USA), principal investigator of the TRANSFORM-AF study. “Given the growing obesity epidemic and the rising prevalence of AF, the TRANSFORM-AF study lays the foundation for a comprehensive, multimodal metabolic approach in conjunction with novel ablation techniques for patients with AF. Further randomised controlled trials are needed to assess the potential benefits of weight-loss doses of GLP-1 RA in this patient population.”
